1. Project Summary. This project aims to improve hearing restoration for severely and profoundly deaf people. The present-day standard of care for restoration of hearing is a cochlear implant (CI), consisting of 16- 22 metal electrodes inserted into the scala tympani of the cochlea. Most CI users can expect to achieve reasonable speech reception in quiet environments. Performance is unsatisfactory, however, in everyday complex auditory scenes containing background noise and competing talkers, as in restaurants and in busy offices and classrooms. Also, CI users have only limited sensitivity to cycle-by-cycle temporal fine structure of sounds, which underlies temporal pitch perception. The impaired pitch perception exacerbates the problems of hearing in complex scenes, impairs voice recognition and sensitivity to the emotional content of speech, limits music appreciation, and degrades understanding of Mandarin and other tonal languages. We have shown in short-term studies in anesthetized cats that a penetrating intraneural (IN) electrode array inserted into the cochlear nerve can overcome many limitations of a CI. In particular, an IN electrode can selectively activate low-frequency cochlear and brainstem pathways that are specialized for transmission of temporal fine structure information. We now wish to translate IN stimulation to human trials. Specifically, we propose to test the feasibility of an implanted prosthesis; our working name for the device is ?CI+1?. The CI+1 consists of 15 channels of a 16-channel Advanced Bionics CI combined with a single-channel iridium electrode that will penetrate the cochlear nerve to target low-frequency cochlear nerve fibers. The iridium electrode is equivalent to one shank of the 8-10 shank penetrating auditory brainstem implant that has been used in FDA-approved clinical trials. Specific Aim 1 is to test the safety and efficacy of 6-month implantations of the CI+ 1 in cats, with daily stimulation. We will measure the electrically evoked auditory brainstem response (eABR) at 2-wk intervals to track any changes in stimulation threshold. Then, in a terminal experiment involving recordings along the tonotopic axis of the inferior colliculus, we will assess spread of excitation and transmission of temporal information by the intrascalar and IN electrodes. Specific Aim 2 is to evaluate short-term IN stimulation in human patients who are undergoing surgery to resect vestibular schwannomas. Specific Aim 3 is to evaluate optimal surgical approaches for CI+1 implantation using studies of cadaveric human temporal bones. Early in the 5th year of funding, we aim to have completed the necessary background studies and to apply for an investigational device exemption from the FDA that will permit translation of the CI+1 to the first human trials. We anticipate that the CI+1 will offer the first human volunteers essentially all the benefits of a conventional CI plus enhanced sensitivity to low-frequency sounds and enhanced pitch perception. In clinical applications, the CI+1 might initially be favored for certain applications, but in principle the device would be a preferred alternative for nearly every candidate for cochlear implantation.